Days Of Abstinence Research Articles

The effects of cannabis abstinence on cognition and resting state network activity in people with multiple sclerosis: A preliminary study

We previously reported that people with multiple sclerosis (pwMS) who have been using cannabis frequently over many years can have significant cognitive improvements accompanied by concomitant task-specific changes in brain activation following 28 days of cannabis abstinence. We now hypothesize that the default Mode Network (DMN), known to modulate cognition, would also show an improved pattern of activation align with cognitive improvement following 28 days of drug abstinence. Thirty three cognitively impaired pwMS who were frequent cannabis users underwent a neuropsychological assessment and fMRI at baseline. Individuals were then assigned to a cannabis continuation (CC, n = 15) or withdrawal (CW, n = 18) group and the cognitive and imaging assessments were repeated after 28 days. Compliance with cannabis withdrawal was checked with regular urine monitoring. Following acquisition of resting state fMRI (rs-fMRI), data were processed using independent component analysis (ICA) to identify the DMN spatial map. Between and within group analyses were carried out using dual regression for voxel-wise comparisons of the DMN. Clusters of voxels were considered statistically significant if they survived threshold-free cluster enhancement (TFCE) correction at p < 0.05. The two groups were well matched demographically and neurologically at baseline. The dual regression analysis revealed no between group differences at baseline in the DMN. By day 28, the CW group in comparison to the CC group had increased activation in the left posterior cingulate, and right, angular gyrus (p < 0.05 for both, TFCE). A within group analysis for the CC group revealed no changes in resting state (RS) networks. Within group analysis of the CW group revealed increased activation at day 28 versus baseline in the left posterior cingulate, right angular gyrus, left hippocampus (BA 36), and the right medial prefrontal cortex (p < 0.05). The CW group showed significant improvements in multiple cognitive domains. In summary, our study revealed that abstaining from cannabis for 28 days reverses activation of DMN activity in pwMS in association with improved cognition across several domains.

Feasibility and acceptability of a novel digital therapeutic combining behavioral and pharmacological treatment for opioid use disorder.

Despite the worsening of the opioid epidemic, access to quality treatment for opioid use disorder (OUD) including buprenorphine remains a challenge. With the onset of the COVID-19 public health emergency, temporary regulatory changes and expanded reimbursement for telehealth services allowed for the rapid expansion of remote treatment for OUD and increased access to buprenorphine, but limited research exists to support this revolutionary shift in care delivery. This study evaluates the feasibility and acceptability of a novel digital therapeutic intervention for OUD combining buprenorphine and behavioral therapy. Adults (n = 27) with OUD received treatment with daily sublingual buprenorphine and psychosocial treatment delivered digitally via a smartphone app over 12 weeks. Participants were evaluated monthly for continued opioid use, medication adherence, anxiety and depression indicators, abstinence self-efficacy, craving, and overall well-being, as well as a one-time measure of treatment acceptability. Participants reported increased opioid abstinence days from baseline (M = 8.2, SD = 8.6) to 12 weeks per 30 days (M = 24.9, SD = 10.1), t(20) = -6.5, p < .000, with strong medication adherence across study waves (96.2%). Anxiety and depression indicators, and opioid craving significantly decreased, and abstinence self-efficacy and overall well-being significantly increased following the intervention. Participants also demonstrated high rates of treatment engagement. As current public health emergency regulatory changes are reviewed for permanency, this feasibility and acceptability study of a novel digital therapeutic intervention for OUD including buprenorphine adds to the growing evidence that supports maintaining telehealth access for quality OUD treatment.

Impact of Shorter Abstinence Periods on Semen Parameters: A Systematic Review and Meta-Analysis.

The success of assisted reproductive technology (ART) relies heavily on semen parameters, and it is influenced by the length of the abstinence period. The World Health Organization (WHO) recommends a 2- to 7-day abstinence period. Even so, efficacy is still suboptimal. Thus, this study aims to determine whether shorter abstinence periods (<2 days) can improve semen parameters. This study is a systematic review and meta-analysis. A literature search was performed across five databases: PubMed, Embase, ProQuest, Scopus, and Wiley Online Library using the PICO format. Retrieved articles were assessed according to eligibility criteria and the PRISMA flow diagram. Those eligible for quantitative analysis were assessed using forest plots. Risks of bias were tested using the Newcastle-Ottawa Scale. A total of 22 studies and 31,640 samples were included. Studies showed that short abstinence periods significantly reduced semen volume (mean difference [MD] -0.83, p<0.01), sperm concentration (MD -8.39, p<0.01), and DNA fragmentation (MD -3.82, p<0.01). No differences in sperm morphology were identified. Meanwhile, the overall effect for total (MD 2.30, p<0.05) and progressive motile sperm (MD 2.18, p<0.01) was significantly increased. Subgroup analysis on oligospermia patients revealed a significant increase in normal sperm morphology (MD 1.64, p<0.01) along with reduced DNA fragmentation (MD -3.30, p<0.05). However, no significant changes were seen among other sperm parameters. In conclusion, our findings suggest a shorter abstinence period could be beneficial due to its effect on sperm motility and DNA fragmentation. Additionally, oligospermia patients will benefit from improved sperm morphology. These findings can provide insight for future guidelines to promote a shorter abstinence period for improving ART outcomes.

Effectiveness of the QuitSure Smartphone App for Smoking Cessation: Findings of a Prospective Single Arm Trial.

Digital therapies, especially smartphone apps for active and continuous smoking cessation support, are strongly emerging as an alternative smoking cessation therapy. In the Indian context, there is a growing interest in the use of app-based smoking cessation programs; however, there is limited evidence regarding their effectiveness in achieving long-term continuous abstinence. This study aimed to evaluate the long-term abstinence effect (up to 30-d abstinence postprogram completion) of a smartphone app, QuitSure, for smoking cessation in active smokers from India. In this prospective single-arm study, participants who signed up for the QuitSure app were enrolled in this study. The primary end point was the prolonged abstinence (PA) rate from weeks 1 to 4 (day 7 to day 30). Furthermore, data for withdrawal symptoms, relapse reasons, and reasons for not continuing the program were also assessed. The quit rate was calculated considering only the participants who followed up and completed the survey sent to them (per protocol) at day 7 and at day 30, respectively. The PA rate at day 7 was found to be 64.5% (111/172; 95% CI 56% to 72%), and the PA rate at day 30 was found to be 55.8% (72/129; 95% CI 45% to 65%). Within the 7-day abstinence period, 60.4% (67/111) of the participants did not have any withdrawal symptoms. The most common mild withdrawal symptoms were mild sleep disturbance (21/111, 18.9%), mild digestive changes (19/111, 17.1%), and coughing (17/111, 15.3%). Severe withdrawal symptoms were rare, with only 5.4% (6/111) experiencing them. For those achieving 30-day postprogram abstinence, 85% (61/72) had no mild withdrawal symptoms, and 99% (71/72) had no severe withdrawal symptoms. Among successful quitters at day 7, a total of 72.1% (80/111) reported minimal to no cravings, which increased to 88% (63/72) at day 30. Furthermore, 78% (56/72) of those with PA at day 30 reported no change in weight or reduced weight. Among participants experiencing relapse, 48% (28/58) cited intense cravings, 28% (16/58) mentioned facing a tragedy, and 26% (15/58) reported relapsing due to alcohol consumption. The PA rates as a result of the QuitSure program were found to be better than those reported in the results of other smoking-cessation app programs' studies. The QuitSure app yields high PA rates and ameliorates symptoms associated with smoking cessation. In order to obtain conclusive evidence regarding the effectiveness and efficacy of the QuitSure program, future research should include appropriate control measures. Nevertheless, the QuitSure program can serve as a valuable adjunct to a conventional smoking cessation treatment program to aid sustained abstinence.

Oral self-administration of pregabalin in a mouse model and the resulting drug addiction features

Prescription drug abuse is an issue that is rapidly growing globally. Pregabalin, an anticonvulsant, analgesic, and anxiolytic medication, is effective in the management of multiple neurological disorders; however, there is increasing concern regarding its widespread illicit use. It has been previously reported in mice that pregabalin can induce conditioned place preference. In this current investigation, the potential of pregabalin to elicit free-choice drinking in a mouse model of drug addiction, and its effect on recognition and withdrawal behaviors after forced abstinence, were studied. Twenty-two male BALB/c mice were randomly divided into three groups (n = 7–8/group); control, pregabalin-30, and pregabalin-60. The study had three phases: habituation (days 1–5) with free water access, free-choice drinking (days 6–13) with pregabalin groups receiving one water and one pregabalin bottle, and forced abstinence (days 14–21) with free water access. On day 13, the first open field test was conducted, followed by the Novel Object Recognition Test. On day 21, the second open field test was performed, followed by the Tail Suspension Test and Forced Swimming Test. Pregabalin elicited voluntary drinking in the higher-dose group, concurrently causing a decline in recognition memory performance in the novel object recognition test. Moreover, pregabalin induced withdrawal behavior after a period of forced abstinence in the forced swimming and tail suspension tests. This is the first report to establish an animal model of free-choice pregabalin drinking that may be used for further molecular studies and targeted therapy for pregabalin addiction.

The outcome of integrated motivational interviewing and cognitive-behavioral therapy in Egyptian patients with substance use disorder

ObjectivesThe authors aimed to evaluate the outcome of combined motivational interviewing and cognitive-behavioral therapy (MICBT) for substance use disorder compared to the twelve-step facilitation (TSF) therapy in terms of retention in the treatment program, the number of relapses, and the period of abstinence after discharge, coping with craving, and modification of problematic behaviors.MethodThis randomized controlled trial included 60 individuals with a substance use disorder. Participants were randomly allocated to equal groups. The MICBT group received 20 sessions of approximately 90 min of MICBT group therapy. The NA (control) group was assigned 20 narcotic anonymous (NA)-oriented TSF group therapy sessions. The assessment was conducted 3 and 6 months after the intervention.ResultThe implementation of MICBT in a group setting leads to a significant decline in the number of days of drug use in 3 months of follow-up (P = 0.006) and 6 months of follow-up (P < 0.001), an increase in the number of days of abstinence in 3 months of follow-up (P = 0.008) and 6 months of follow-up (P < 0.001), a longer time to the first lapse (P < 0.001), and a higher percentage of attendance days for treatment (P < 0.001) in comparison to NA groups. MICBT intervention was a significant positive predictor of several urge-specific coping strategies and several general strategies for drugs (P < 0.05).ConclusionUsing MICBT in group settings presents several benefits in clinical contexts.

Cannabis cravings predict cigarette use in schizophrenia: a secondary analysis from two cannabis abstinence studies

ABSTRACT Background: People with schizophrenia have high rates of cannabis use disorder (CUD) as well as co-use of tobacco. Tobacco may be used to alleviate cannabis cravings. Objectives: We conducted a secondary analysis of 7 and 28 days of cannabis abstinence from two datasets of participants with CUD with and without schizophrenia to assess cannabis craving, cannabis use in grams per day (GPD) and cigarettes per day (CPD). Methods: We recruited 49 participants (schizophrenia n = 29; control n = 20; 2% female) with CUD. All participants received weekly behavioral support sessions to assist with cannabis abstinence/reduction. GPD and CPD were assessed with the 7-day Timeline Follow-back; the Marijuana Craving Questionnaire (MCQ) assessed compulsivity, emotionality, expectancy and purposefulness subscales. Effects of GPD and MCQ subscales on CPD at days 7 and 28 were assessed with analysis of covariance. Results: At day seven, participants with schizophrenia scored higher on compulsivity (t = 2.72, df = 46.8, p < .01), emotionality (t = 2.48, df = 45.2, p = .02), and purposefulness (t = 2.32, df = 39.41, p = .02) craving subscales than control participants. There was a significant interaction between high purposefulness craving and low GPD on high CPD at day seven (F1,23 = 4.76, p = .039) and day 28 (F1,13 = 7.02 p = .02) in schizophrenia participants but not control participants. Conclusion: We found preliminary evidence that due to cannabis craving intensity, people with schizophrenia and CUD may use more cigarettes when reducing cannabis use, as compared to CUD participants without schizophrenia. Strategies to manage cannabis craving and avoid increasing tobacco use will be useful to implement in intervention strategies. Clinical Trial Name Effects of Repetitive Transcranial Magnetic Stimulation (rTMS) on Cannabis Use and Cognitive Outcomes in Schizophrenia URL: www.clinicaltrials.gov; Registration Number: NCT03189810;

Relative Efficacy of an Acceptance and Commitment Therapy-Based Smartphone App with a Standard US Clinical Practice Guidelines-Based App for Smoking Cessation in Dual Users of Combustible and Electronic Cigarettes: Secondary Findings from a Randomized Trial

Background While smartphone apps for smoking cessation have shown promise for combustible cigarette smoking cessation, their efficacy in helping dual users of combustible and electronic cigarettes (e-cigarettes) to quit cigarettes remains unknown. This study utilized data from a randomized trial to determine if an Acceptance and Commitment Therapy (ACT)-based app (iCanQuit) was more efficacious than a US Clinical Practice Guidelines-based app (QuitGuide) for combustible cigarette smoking cessation among 575 dual users. Methods The primary cessation outcome was self-reported, complete-case 30-day abstinence from combustible cigarettes at 12 months. Logistic regression assessed the interaction between dual use and treatment arm on the primary outcome in the full trial sample (N = 2,415). We then compared the primary outcome between arms among dual users (iCanQuit: n = 297; QuitGuide: n = 178). Mediation analyses were conducted to explore mechanisms of action of the intervention: acceptance of cues to smoke and app engagement. Results: There was an interaction between dual use of combustible and e-cigarettes and treatment arm on the primary outcome (p = 0.001). Among dual users, 12-month abstinence from cigarettes did not differ between arms (23% for iCanQuit vs. 27% for QuitGuide, p = 0.40). Mediation analysis revealed a significant positive indirect effect of the iCanQuit app on 12-month abstinence from cigarettes through acceptance of emotions that cue smoking (p = 0.004). Conclusions Findings from this study of dual users of combustible and e-cigarettes showed no evidence of a difference in quit rates between arms. Acceptance of emotions that cue smoking is a potential mechanism contributing to cigarette smoking abstinence among dual users.

Using alcohol biosensors and biomarkers to measure changes in drinking: Associations between transdermal alcohol concentration, phosphatidylethanol, and self-report in a contingency management study of persons with and without HIV.

Alcohol use can be measured in many ways, including objectively through transdermal alcohol biosensors (e.g., transdermal alcohol concentration; TAC) or blood biomarkers (e.g., phosphatidylethanol; PEth), or subjectively through self-report (e.g., with the timeline followback; TLFB). However, it is unclear which measures best indicate changes in alcohol use within individuals following intervention, and if they have concurrent validity. In the context of contingency management (CM) with a goal of 30-day abstinence (n = 45, 60% male, 80% Black; Mage = 56.7; 58% with HIV), we examined relationships among changes in TAC-AUC (area under the curve, reflecting volume consumed), PEth, and self-reported number of drinks. The Secure Continuous Remote Alcohol Monitor Continuous Alcohol Monitoring (SCRAM-CAM) biosensor was used to collect TAC-AUC during a pre-CM period (∼7 days) and over a 30-day CM period. PEth was collected at baseline and 30-day follow-up. Number of drinks was self-reported through a 30-day TLFB at baseline and follow-up. Daily TAC-AUC and number of self-reported drinks were calculated for the pre-CM period and for the last 7 days of the CM period. Linear regression models controlling for baseline values revealed that change in TAC-AUC was significantly associated with change in PEth (β = 0.33, p < .0001) and with change in number of self-reported drinks (β = 0.34, p < .0001). Change in PEth was significantly associated with change in number of self-reported drinks (β = 0.85, p < .0001). We conclude that all three measures may be appropriate for measuring within-person change in alcohol use, while controlling for baseline values, in the context of a study testing an intervention such as CM. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The anterior insula and its projection to amygdala nuclei modulate the abstinence-exacerbated expression of conditioned place preference

RationaleRelapse into substance use is often triggered by exposure to drug-related environmental cues. The magnitude of drug seeking depends on the duration of abstinence, a phenomenon known as the incubation of drug craving. Clinical and preclinical research shows that the insular cortex is involved in substance use disorders and cue-induced drug seeking. However, the role of the insula on memory retrieval and motivational integration for cue-elicited drug seeking remains to be determined.ObjectivesWe investigated the role of the anterior insular cortex (aIC) and its glutamatergic projection to amygdala nuclei (aIC-AMY) on the expression of conditioned place preference (CPP) during early and late abstinence.MethodsMale adult C57BL/6J mice underwent amphetamine-induced CPP, and their preference was tested following 1 or 14 days of abstinence. aIC and aIC-AMY functional role in CPP expression was assessed at both abstinence periods by employing optogenetic silencing and behavioral pharmacology.ResultsCompared to a single day, an exacerbated preference for the amphetamine-paired context was observed after 14 days of abstinence. Photoinhibition of either aIC or aIC-AMY projection reduced CPP expression following late but not early abstinence. Similarly, the antagonism of aIC NMDA receptors reduced CPP expression after 14 days of abstinence but not 1 day.ConclusionsThese results suggest that aIC and its glutamatergic output to amygdala nuclei constitute critical neurobiological substrates mediating enhanced motivational cue reactivity during the incubation of amphetamine craving rather than contextual memory recall. Moreover, cortical NMDA receptor signaling may become sensitized during abstinence, ultimately modulating disproportioned drug seeking.

Do medications increase the efficacy of digital interventions for smoking cessation? Secondary results from the iCanQuit randomized trial.

iCanQuit is a smartphone application (app) proven efficacious for smoking cessation in a Phase III randomized controlled trial (RCT). This study aimed to measure whether medications approved by the US Food and Drug Administration (FDA) for smoking cessation would further enhance the efficacy of iCanQuit, relative to its parent trial comparator-the National Cancer Institute's (NCI's) QuitGuide app. Secondary analysis of the entire parent trial sample of a two-group (iCanQuit and QuitGuide), stratified, doubled-blind RCT. United States. Participants who reported using an FDA-approved cessation medication on their own (n= 619) and those who reported no use of cessation medications (n= 1469). Participants were randomized to receive iCanQuit app or NCI's QuitGuide app. Use of FDA-approved medications was measured at 3 months post-randomization. Smoking cessation outcomes were measured at 3, 6 and 12 months. The primary outcome was 12-month self-reported 30-day point prevalence abstinence (PPA). The data retention rate at the 12-month follow-up was 94.0%. Participants were aged 38.5 years, 71.0% female, 36.6% minority race/ethnicity, 40.6% high school or less education, residing in all 50 US States and smoking 19.2 cigarettes/day. The 29.6% of all participants who used medications were more likely to choose nicotine replacement therapy (NRT; 78.8%) than other cessation medications (i.e. varenicline or bupropion; 18.3 and 10.5%, respectively) and use did not differ by app treatment assignment (all P> 0.05). There was a significant (P= 0.049) interaction between medication use and app treatment assignment on PPA. Specifically, 12-month quit rates were 34% for iCanQuit versus 20% for QuitGuide [odds ratio (OR) = 2.36, 95% confidence interval (CI) = 1.59, 3.49] among participants reporting any medication use, whereas among participants reporting no medication use, quit rates were 28% for iCanQuit versus 22% for QuitGuide (OR = 1.41, 95% CI = 1.09, 1.82). Results were stronger for those using only NRT: 40% quit rates for iCanQuit versus 18% quit rates for QuitGuide (OR = 3.57, 95% CI = 2.20, 5.79). The iCanQuit smartphone app for smoking cessation was more efficacious than the QuitGuide smartphone app, regardless of whether participants used medications to aid cessation. Smoking cessation medications, especially nicotine replacement therapy, might enhance the efficacy of the iCanQuit app.

Extinction and reinstatement of methamphetamine-induced conditioned place preference in zebrafish.

Conditioned place preference (CPP) paradigm in zebrafish has been used to measure drug reward, but there is limited research on CPP reinstatement to determine relapse vulnerability. The present study aimed to investigate extinction and reinstatement of methamphetamine (MA)-induced CPP in zebrafish and evaluate the model's predictive validity. Zebrafish received different doses of MA (0-60 mg/kg) during CPP training. The preferred dose of MA at 40 mg/kg was used for extinction via either confined or nonconfined procedures. The extinguished CPP was reinstated by administering a priming dose of MA (20 mg/kg) or various stressors. To assess persistent susceptibility to reinstatement, MA CPP and reinstatement were retested following 14 days of abstinence. In addition, the effects of SCH23390, naltrexone, and clonidine on MA CPP during acquisition, expression, or reinstatement phases were monitored. MA induced CPP in a dose-dependent manner. Both nonconfined and confined extinction procedures time-dependently reduced the time spent on the MA-paired side. A priming dose of MA, chasing stress, or yohimbine reinstated the extinguished CPP. After 14 days of abstinence, the MA CPP remained extinguished and was significantly reinstated by MA priming or chasing stress. Similar to the observations in rodents, SCH23390 suppressed the acquisition of MA CPP, naltrexone reduced the expression and MA priming-induced reinstatement, while clonidine prevented stress-induced reinstatement of MA CPP. This work expanded the zebrafish CPP paradigm to include extinction and reinstatement phases, demonstrating predictive validity and highlighting its potential as a valuable tool for exploring drug relapse.

Effect of a mindfulness training app on a cigarette quit attempt: an investigator-blinded, 58-county randomized controlled trial.

Cigarette smoking is the leading cause of preventable cancers. A majority of the 34 million people who currently smoke report wanting to quit. Mindfulness training apps offer a guided telehealth intervention to foster individuals' behavioral meditation practice. We present the main outcomes of a parallel-group randomized controlled trial that tested app-based mindfulness training vs attention control on smoking behavior. We enrolled adult residents from across California who smoked daily and were willing to make a quit attempt (N = 213). Participants completed daily sessions in 10-minute segments for 14 consecutive days. Participants then started a quit attempt and reported daily smoking for 28 days following the quit date using the timeline follow-back measure. Seven-day point-prevalence abstinence for each week during the 4-week quit period ranged from 21.8% to 27.7% for app-based mindfulness training and 17.9% to 19.6% for controls. The intention-to-treat sample revealed that app-based mindfulness training outperformed controls on the proportion of abstinence days during the quit period (odds ratio = 2.00, 95% confidence interval = 1.03 to 3.87, P = .041). Although the 7-day point prevalence abstinence for week 4 favored app-based mindfulness training, significance was not reached (odds ratio = 1.65, 95% confidence interval = 0.84 to 3.23, P = .148). The mean number of cigarettes smoked per day among smokers was 4.95 for app-based mindfulness training vs 5.69 for controls (odds ratio = 0.81, 95% confidence interval = 0.71 to 0.92, P = .002), suggesting harm reduction in continued smokers. A mindfulness training app prescribed for 2 weeks leading up to a quit date showed an advantage over controls for total abstinence days and fewer cigarettes smoked in a diverse sample consisting of urban and rural residents. These findings yield implications for the use of apps to reduce exposure to the carcinogenic properties of cigarette smoke.

Effects of a short abstinence period on sperm quality in oligozoospermic men.

The aim of this study was to compare semen parameters and sperm DNA fragmentation (SDF) and explore the relationship between semen parameters and SDF between 2 and 7 days of abstinence and a short abstinence period (within 4 hours) in oligozoospermic infertile patients. Two semen samples were collected from infertile oligozoospermic men (n=34) after an abstinence period of 2 to 7 days and within 4 hours, respectively. Sperm parameters were compared between the two abstinence duration groups, including semen volume, sperm concentration, total sperm count, sperm motility, total motile sperm count (TMSC), morphology, and SDF. The semen volume, concentration, and total sperm count were significantly decreased after 4 hours of abstinence than after 2 to 7 days of abstinence, with median differences of 1.2 mL (p<0.001), 2×106/mL (p=0.011), and 9.6×106/ejaculation (p<0.001), respectively. TMSC was significantly lower after a short abstinence, with a median difference of 4.24×106/ejaculate (p<0.001). However, there were no significance differences in the percentage of motility, the SDF, and the percentage of sperm with normal morphology. Interestingly, volume, concentration, total sperm count, sperm motility, and SDF, but not TMSC, exhibited significant linear correlations between the two abstinence groups in univariate regression analysis, except for TMSC. In oligozoospermic men, the volume, concentration, and total sperm count were significantly lower after a short abstinence period, but without adverse effects on sperm motility and SDF.

A Bayesian zero-inflated beta-binomial model for longitudinal data with group-specific changepoints.

Timeline followback (TLFB) is often used in addiction research to monitor recent substance use, such as the number of abstinent days in the past week. TLFB data usually take the form of binomial counts that exhibit overdispersion and zero inflation. Motivated by a 12-week randomized trial evaluating the efficacy of varenicline tartrate for smoking cessation among adolescents, we propose a Bayesian zero-inflated beta-binomial model for the analysis of longitudinal, bounded TLFB data. The model comprises a mixture of a point mass that accounts for zero inflation and a beta-binomial distribution for the number of days abstinent in the past week. Because treatment effects appear to level off during the study, we introduce random changepoints for each study group to reflect group-specific changes in treatment efficacy over time. The model also includes fixed and random effects that capture group- and subject-level slopes before and after the changepoints. Using the model, we can accurately estimate the mean trend for each study group, test whether the groups experience changepoints simultaneously, and identify critical windows of treatment efficacy. For posterior computation, we propose an efficient Markov chain Monte Carlo algorithm that relies on easily sampled Gibbs and Metropolis-Hastings steps. Our application shows that the varenicline group has a short-term positive effect on abstinence that tapers off after week 9.

The effectiveness of a telephone smoking cessation program in mental health clinic patients by level of mental well-being and functioning: a secondary data analysis of a randomized clinical trial

BackgroundFew studies have examined the effectiveness of telephone smoking cessation interventions by severity of behavioral health symptoms. Using data from a telephone counseling study, we examined whether abstinence rates varied by level of behavioral health symptoms.MethodsThe parent study recruited adults who smoke cigarettes (N = 577) referred by mental health providers at six Veterans Health Administration facilities. Participants were randomized to specialized telephone counseling (intervention) or state Quitline referral (control). Participants completed assessments at baseline and 6 months, including the BASIS-24, a self-report measure of behavioral health symptoms and functioning. We used the BASIS-24 median to dichotomize participants as having high or low scores. The primary outcome was 30-day self-reported abstinence at 6 months. We compared groups on outcomes by logistic regression and performed an interaction effect analysis between treatment assignment and groups.ResultsAt baseline, those with high behavioral health symptoms scores reported heavier nicotine dependence and more sedative and/or antidepressant use, compared to participants with low behavioral health symptoms. At 6 months, participants with low behavioral health symptoms scores in the intervention reported higher rates of 30-day abstinence compared to those in the control arm (26% vs 13%, OR = 2.3, 95% CI = 1.8, 2.9). People with high behavioral health symptoms scores reported no difference in 30-day abstinence between the treatment assignments at 6 months (12% vs. 13%, OR = 1.1, 95% CI = 0.6, 2.0).ConclusionsOnly participants with low behavioral health symptoms scores reported higher abstinence rates in the intervention compared to the state Quitline. Future research can examine alternative approaches for people with worse mental well-being and functioning.Trial registrationThe parent study is registered at www.clinicaltrials.gov NCT00724308.

Six-month course and outcome of treatment-seeking individuals with alcohol dependence syndrome.

Despite the availability of several pharmacological and nonpharmacological treatments, a significant proportion of patients with alcohol dependence relapse to alcohol use after treatment. The objectives of this study were to determine the 6-month course and outcome in treatment-seeking individuals with alcohol dependence syndrome and to determine the sociodemographic and clinical correlates of the outcome in these patients. A longitudinal observational study was conducted in treatment-seeking male patients with alcohol dependence syndrome. Baseline sociodemographic and clinical details were gathered using a structured pro forma. The patients were followed up at 2 weeks, 1 month, 3 months, and 6 months. During the follow-up evaluation, abstinence status, number of abstinent days, and number of heavy drinking days were noted. Logistic regression was conducted to evaluate the factors associated with abstinence at 6 months. Ninety-four patients were recruited for the study. The mean age of the participants was 43.98 years (standard deviation (SD) 10.68). Two patients were lost to follow-up. At the end of 2 weeks, 74 (80.43%) out of 92 participants remained abstinent. At the end of 1 month and 3 months, 59 (64.13%) and 38 (41.3%) participants of 92 were abstinent, respectively. At the end of 6 months, 26 (30.23%) of 86 patients were abstinent. Among those who were not abstinent at 6 months, the mean number of abstinent days was 113 (SD 51.62) days and the mean number of heavy drinking days was 56 (SD 51.62) days. Outpatients were found to have 2.91 times higher odds of remaining abstinent at 6 months when compared to inpatients. Nearly one-third of treatment-seeking patients with alcohol dependence syndrome remained abstinent at the end of 6 months. The locus of treatment was associated with abstinence at 6 months.

62 Exploration of Sex Differences in Cannabis Use Patterns, Driving Performance, and Subjective Intoxication Effects

Objective:Although some animal research suggests possible sex differences in response to THC exposure (e.g., Cooper &amp; Craft, 2018), there are limited human studies. One study found that among individuals rarely using cannabis, when given similar amounts of oral and vaporized THC females report greater subjective intoxication compared to males (Sholler et al., 2020). However, in a study of daily users, females reported indistinguishable levels of intoxication compared to males after smoking similar amounts (Cooper &amp; Haney, 2014), while males and females using 1–4x/week showed similar levels of intoxication, despite females having lower blood THC and metabolite concentrations (Matheson et al., 2020). It is important to elucidate sex differences in biological indicators of cannabis intoxication given potential driving/workplace implications as states increasingly legalize use. The current study examined if when closely matching males and females on cannabis use variables there are predictable sex differences in residual whole blood THC and metabolite concentrations, and THC/metabolites, subjective appraisals of intoxication, and driving performance following acute cannabis consumption.Participants and Methods:The current study was part of a randomized clinical trial (Marcotte et al., 2022). Participants smoked ad libitum THC cigarettes and then completed driving simulations, blood draws, and subjective measures of intoxication. The main outcomes were the change in Composite Drive Score (CDS; global measure of driving performance) from baseline, whole blood THC, 11-OH-THC, and THC-COOH levels (ng/mL), and subjective ratings of how “high” participants felt (0 = not at all, 100 = extremely). For this analysis of participants receiving active THC, males were matched to females on 1) estimated THC exposure (g) in the last 6 months (24M, 24F) or 2) whole blood THC concentrations immediately post-smoking (23M, 23F).Results:When matched on THC exposure in the past 6 months (overall mean of 46 grams; p = .99), there were no sex differences in any cannabinoid/metabolite concentrations at baseline (all p &gt; .83) or after cannabis administration (all p &gt; .72). Nor were there differences in the change in CDS from pre-to-post-smoking (p = .26) or subjective “highness” ratings (p = .53). When matched on whole blood THC concentrations immediately after smoking (mean of 34 ng/mL for both sexes, p = .99), no differences were found in CDS change from pre-to-post smoking (p = .81), THC metabolite concentrations (all p &gt; .25), or subjective “highness” ratings (p = .56). For both analyses, males and females did not differ in BMI (both p &gt; .7).Conclusions:When male/female cannabis users are well-matched on use history, we find no significant differences in cannabinoid concentrations following a mean of 5 days of abstinence, suggesting that there are no clear biological differences in carryover residual effects. We also find no significant sex differences following ad libitum smoking in driving performance, subjective ratings of “highness,” nor whole blood THC and metabolite concentrations, indicating that there are no biological differences in acute response to THC. This improves upon previous research by closely matching participants over a wider range of use intensity variables, although the small sample size precludes definitive conclusions.

Varenicline Combined With Oral Nicotine Replacement Therapy and Smartphone-Based Medication Reminders for Smoking Cessation: Feasibility Randomized Controlled Trial.

Varenicline and oral nicotine replacement therapy (NRT) have each been shown to increase the likelihood of smoking cessation, but their combination has not been studied. In addition, smoking cessation medication adherence is often poor, thus, challenging the ability to evaluate medication efficacy. This study examined the effects of combined varenicline and oral NRT and smartphone medication reminders on pharmacotherapy adherence and smoking abstinence among adults enrolled in smoking cessation treatment. A 2×2 factorial design was used. Participants (N=34) were randomized to (1) varenicline + oral NRT (VAR+NRT) or varenicline alone (VAR) and (2) smartphone medication reminder messages (REM) or no reminder messages (NREM) over 13 weeks. Participants assigned to VAR+REM received varenicline reminder prompts, and those assigned to VAR+NRT+REM also received reminders to use oral NRT. The other 2 groups (VAR+NREM and VAR+NRT+NREM) did not receive medication reminders. Participants were not blinded to intervention groups. All participants received tobacco cessation counseling. Smartphone assessments of smoking as well as varenicline and NRT use (if applicable) were prompted daily through the first 12 weeks after a scheduled quit date. Descriptive statistics were generated to characterize the relations between medication and reminder group assignments with daily smoking, daily varenicline adherence, and daily quantity of oral NRT used. Participants completed follow-up assessments for 26 weeks after the quit date. Participants were predominantly White (71%), and half were female (50%). On average, participants were 54.2 (SD 9.4) years of age, they smoked an average of 19.0 (SD 9.0) cigarettes per day and had smoked for 34.6 (SD 12.7) years. Descriptively, participants assigned to VAR+NRT reported more days of smoking abstinence compared to VAR (29.3 vs 26.3 days). Participants assigned to REM reported more days of smoking abstinence than those assigned to NREM (40.5 vs 21.8 days). Participants assigned to REM were adherent to varenicline on more days compared to those assigned to NREM (58.6 vs 40.5 days), and participants assigned to VAR were adherent to varenicline on more days than those assigned to VAR + NRT (50.7 vs 43.3 days). In the subsample of participants assigned to VAR+NRT, participants assigned to REM reported more days where ≥5 pieces of NRT were used than NREM (14.0 vs 7.4 days). Average overall medication adherence (assessed via the Medication Adherence Questionnaire) showed the same pattern as the daily smartphone-based adherence assessments. Preliminary findings indicated that smoking cessation interventions may benefit from incorporating medication reminders and combining varenicline with oral NRT, though combining medications may be associated with poorer adherence. Further study is warranted. ClinicalTrials.gov NCT03722966; https://classic.clinicaltrials.gov/ct2/show/NCT03722966.

Effect of ejaculatory abstinence period on fertilization and clinical outcomes in ICSI cycles: a retrospective analysis

Does ejaculatory abstinence impact fertilization outcomes in intracytoplasmic sperm injection (ICSI) cycles in infertile couples? This single-centre retrospective observational study included 6919 ICSI cycles from 2013 to 2022. The primary outcome was the assessment of oocyte fertilization, measured in terms of the rate of formation of two-pronuclear (2PN), 3PN and 1PN zygotes. Secondary outcomes were blastulation, cumulative positive β-human chorionic gonadotrophin test and clinical pregnancy rates. Relationships between ejaculatory abstinence and fertilization outcomes, and ejaculatory abstinence and clinical outcomes were evaluated with multivariable analysis, including possible confounders. A positive association was observed between ejaculatory abstinence and semen sample volume (P < 0.001), sperm concentration (P < 0.001) and total motile sperm count (P < 0.001). No association was found between the 1PN zygote rate and ejaculatory abstinence (P = 0.97). Conversely, for each additional day of ejaculatory abstinence, the likelihood of obtaining 2PN zygotes from all inseminated oocytes decreased by 3% [adjusted odds ratio (aOR) 0.97, 95% CI 0.94-0.99], whilst the likelihood of obtaining 3PN zygotes from all inseminated oocytes increased significantly by 14% (aOR 1.14, 95% CI 1.07-1.22). No significant associations were found between ejaculatory abstinence and blastulation, cumulative pregnancy or miscarriage rates. A longer ejaculatory abstinence period significantly decreases the rate of 2PN zygotes, and increases the rate of 3PN zygotes without directly affect blastulation and pregnancy rates.